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A comprehensive phytochemical investigation of the twigs/leaves and flower buds of Kolkwitzia amabilis, a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (1–4 and 7–13), 20 triterpenoids (5, 6, and 14–31), and 8 phenylpropanoids (32–39). Among these, amabiliosides A (1) and B (2) represent previously undescribed bis-iridoid glycosides, while amabiliosides C (3) and D (4) feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro-β-carboline-5-carboxylic acid moiety. Amabiliacids A (5) and B (6) are 24-nor-ursane-type triterpenoids characterized by an uncommon ∆11,13(18) transannular double bond. Their chemical structures and absolute configurations were elucidated through spectroscopic data and electronic circular dichroism analyses. Compound 2 exhibited a moderate inhibitory effect against acetyl CoA carboxylase 1 (ACC1), with an IC50 value of 9.6 μM. Lonicejaposide C (8), 3β-O-trans-caffeoyl-olean-12-en-28-oic acid (29), and (23E)-coumaroylhederagenin (31) showed notable inhibitory effects on ATP-citrate lyase (ACL), with IC50 values of 3.6, 1.6, and 4.7 μM, respectively. Additionally, 3β-acetyl-ursolic acid (17) demonstrated dual inhibitory activity against both ACC1 and ACL, with IC50 values of 10.3 and 2.0 μM, respectively. The interactions of the active compounds with ACC1 and ACL enzymes were examined through molecular docking studies. From a chemotaxonomic perspective, the isolation of bis-iridoid glycosides in this study may aid in clarifying the taxonomic relationship between the genera Kolkwitzia and Lonicera within the Caprifoliaceae family. These findings highlight the importance of conserving plant species with unique and diverse secondary metabolites, which could serve as potential sources of new therapeutic agents for treating ACC1/ACL-associated diseases.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had “triple-furrowed” tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

Objective: Mumps is a seasonal infectious disease, always occurring in winter and spring. In this study, we aim to analyze its epidemiological characteristics, transmissibility, and its correlation with meteorological variables. Method: A seasonal Susceptible–Exposed–Infectious/Asymptomatic–Recovered model and a next-generation matrix method were applied to estimate the time-dependent reproduction number (Rt). Results: The seasonal double peak of annual incidence was mainly in May to July and November to December. There was high transmission at the median of Rt = 1.091 (ranged: 0 to 4.393). Rt was seasonally distributed mainly from February to April and from September to November. Correlations were found between temperature (Pearson correlation coefficient [r] ranged: from 0.101 to 0.115), average relative humidity (r = 0.070), average local pressure (r = -0.066), and the number of new cases. In addition, average local pressure (r = 0.188), average wind speed (r = 0.111), air temperature (r ranged: -0.128 to -0.150), average relative humidity (r = -0.203) and sunshine duration (r = -0.075) were all correlated with Rt. Conclusion: A relatively high level of transmissibility has been found in Xiamen City, leading to a continuous epidemic of mumps. Meteorological factors, especially air temperature and relative humidity, may be more closely associated with mumps than other factors.

Abstract Background Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China. Methods We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (R eff) was used to estimate the transmission interaction in different age groups. Results A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (R eff = 4.28), followed by group 2 to 3 (R eff = 2.61), and group 2 to 4 (R eff = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45–64 years old. Conclusions Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15–64 years should first be vaccinated to prevent transmission in China. Graphical Abstract

Abstract Many end-to-end approaches have been proposed to detect predefined keywords. For scenarios of multi-keywords, there are still two bottlenecks that need to be resolved: (1) the distribution of important data that contains keyword(s) is sparse, and (2) the timestamps of the detected keywords are inaccurate. In this paper, to alleviate the first issue and further improve the performance of the end-to-end ASR front-end, we propose the biased loss function for guiding the recognizer to pay more attention to the speech segments containing the predefined keywords. As for the second issue, we solve this problem by modifying the force alignment applied to the end-to-end ASR front-end. To get the frame-level alignment, we utilize a Gaussian Mixture Model-Hidden Markov Model (GMM-HMM) based acoustic model (AM) for auxiliary. The proposed system is evaluated in the OpenSAT20 held by the National Institute of Standards and Technology (NIST). The performance of our end-to-end KWS system is comparable to the conventional hybrid KWS system, sometimes even slightly better. With fusion results of the end-to-end and conventional KWS systems, we won the first prize in the KWS track. On the dev dataset (a part of SAFE-T corpus), the system outperforms the baseline by a large margin, i.e., our system with GMM-HMM aligner has a lower segmentation-aware word error rates (relatively 7.9–19.2% decrease) and higher overall Actual term-weighted values (relatively 3.6–11.0% increase), which demonstrates the effectiveness of the proposed method. For more precise alignments, we can use DNN-based AM as alignmentor at the cost of more computation.

Abstract Background Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province. Methods We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness. Results From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R 2 = 0.655, P

Abstract Background Novel coronavirus disease 2019 (COVID-19) causes an immense disease burden. Although public health countermeasures effectively controlled the epidemic in China, non-pharmaceutical interventions can neither be maintained indefinitely nor conveniently implemented globally. Vaccination is mainly used to prevent COVID-19, and most current antiviral treatment evaluations focus on clinical efficacy. Therefore, we conducted population-based simulations to assess antiviral treatment effectiveness among different age groups based on its clinical efficacy. Methods We collected COVID-19 data of Wuhan City from published literature and established a database (from 2 December 2019 to 16 March 2020). We developed an age-specific model to evaluate the effectiveness of antiviral treatment in patients with COVID-19. Efficacy was divided into three types: (1) viral activity reduction, reflected as transmission rate decrease [reduction was set as v (0–0.8) to simulate hypothetical antiviral treatments]; (2) reduction in the duration time from symptom onset to patient recovery/removal, reflected as a 1/γ decrease (reduction was set as 1–3 days to simulate hypothetical or real-life antiviral treatments, and the time of asymptomatic was reduced by the same proportion); (3) fatality rate reduction in severely ill patients (f c ) [reduction (z) was set as 0.3 to simulate real-life antiviral treatments]. The population was divided into four age groups (groups 1, 2, 3 and 4), which included those aged ≤ 14; 15–44; 45–64; and ≥ 65 years, respectively. Evaluation indices were based on outbreak duration, cumulative number of cases, total attack rate (TAR), peak date, number of peak cases, and case fatality rate (f). Results Comparing the simulation results of combination and single medication therapy s, all four age groups showed better results with combination medication. When 1/γ = 2 and v = 0.4, age group 2 had the highest TAR reduction rate (98.48%, 56.01–0.85%). When 1/γ = 2, z = 0.3, and v = 0.1, age group 1 had the highest reduction rate of f (83.08%, 0.71–0.12%). Conclusions Antiviral treatments are more effective in COVID-19 transmission control than in mortality reduction. Overall, antiviral treatments were more effective in younger age groups, while older age groups showed higher COVID-19 prevalence and mortality. Therefore, physicians should pay more attention to prevention of viral spread and patients deaths when providing antiviral treatments to patients of older age groups.

Abstract Background The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called 2019-nCoV) causes different morbidity risks to individuals in different age groups. This study attempts to quantify the age-specific transmissibility using a mathematical model. Methods An epidemiological model with five compartments (susceptible–exposed–symptomatic–asymptomatic–recovered/removed [SEIAR]) was developed based on observed transmission features. Coronavirus disease 2019 (COVID-19) cases were divided into four age groups: group 1, those ≤ 14 years old; group 2, those 15 to 44 years old; group 3, those 45 to 64 years old; and group 4, those ≥ 65 years old. The model was initially based on cases (including imported cases and secondary cases) collected in Hunan Province from January 5 to February 19, 2020. Another dataset, from Jilin Province, was used to test the model. Results The age-specific SEIAR model fitted the data well in each age group (P

Abstract Background Developing countries exhibit a high disease burden from shigellosis. Owing to the different incidences in males and females, this study aims to analyze the features involved in the transmission of shigellosis among male (subscript m) and female (subscript f) individuals using a newly developed sex-based model. Methods The data of reported shigellosis cases were collected from the China Information System for Disease Control and Prevention in Hubei Province from 2005 to 2017. A sex-based Susceptible–Exposed–Infectious/Asymptomatic–Recovered (SEIAR) model was applied to explore the dataset, and a sex-age-based SEIAR model was applied in 2010 to explore the sex- and age-specific transmissions. Results From 2005 to 2017, 130 770 shigellosis cases (including 73 981 male and 56 789 female cases) were reported in Hubei Province. The SEIAR model exhibited a significant fitting effect with the shigellosis data (P

Abstract Background As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. Methods In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R 0) from the RP model to assess the transmissibility of the SARS-CoV-2. Results The value of R 0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. Conclusions Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.

Background: With the progress of urbanization, the mobility of people has gradually increased, which has led to the further spread of dengue fever. This study evaluated the transmissibility of dengue fever within districts and between different districts in Zhanjiang City to provide corresponding advice for cross-regional prevention and control. Methods: A mathematical model of transmission dynamics was developed to explore the transmissibility of the disease and to compare that between different regions. Results: A total of 467 DF cases (6.38 per 100,000 people) were reported in Zhanjiang City in 2018. In the model, without any intervention, the number of simulated cases in this epidemic reached about 950. The dengue fever transmissions between districts varied within and between regions. When the spread of dengue fever from Chikan Districts to other districts was cut off, the number of cases in other districts dropped significantly or even to zero. When the density of mosquitoes in Xiashan District was controlled, the dengue fever epidemic in Xiashan District was found to be significantly alleviated. Conclusions: When there is a dengue outbreak, timely measures can effectively control it from developing into an epidemic. Different prevention and control measures in different districts could efficiently reduce the risk of disease transmission.

At present, ischemic stroke seriously affects people's life and health, and its occurrence, development and therapeutic effect are affected by many factors. With the deep research on ischemic cerebral apoplexy disease, people have a deeper understanding of its virulence genes. The apolipoprotein E genotype is the research focus recently, its genetic type is not only involved in the occurrence and development of ischemic cerebral apoplexy, but also causes different therapeatic effects. In this paper, we reviewed the relationship between apolipoprotein E gene polymorphism and lipid metabolism and atherosclerosis in ischemic stroke, as well as the differences in the therapeutic effects of thrombolysis, thrombectomy and lipid-lowering among different genotypes. [ABSTRACT FROM AUTHOR]

The orientation and predissociation dynamics of the NaI molecule are studied by using a time-dependent wavepacket method. The NaI molecule is first pre-oriented by a single-cycle pulse (SCP) in terahertz (THz) region and then predissociated by a femtosecond pump pulse. The influence of the molecular field-free orientation on the predissociation dynamics is studied in detail. We calculate the radial and angular distributions, the molecular orientation degrees, and the time-dependent populations for both the ground and excited electronic states. It is found that the pre-orientation affects the angular distributions significantly, and that it has weak influence on the radial distributions. By varying the delay time between the THz SCP and the pump pulse, the angular distribution of the fragments from the predissociation can be manipulated. [ABSTRACT FROM AUTHOR]

The formation of ultracold Cs2 molecules via photoassociation (PA) with a spectral π -jump laser pulse is theoretically investigated by solving the time-dependent Schrodinger equation using the mapped Fourier grid method. Numerical calculations show that the population distributions of associated molecules mainly result from the off-resonant excitation of the π-jump laser pulse. Compared with the transform-limited pulse, an efficient population accumulation in the PA process is achieved with the π -jump pulse. An oscillation pattern appears in the population on the vibrational levels of the 0g- state owing to the action of the post-half-pulse in the π-jump pulse. The PA efficiency is related to the Rabi angle of the laser pulse. A π -jump pulse can be used to enhance more effectively the PA efficiency than a transform-limited pulse with the same Rabi angle. [ABSTRACT FROM AUTHOR]